Abstract

Latent or low-level persistent reservoirs of HIV-1 may be the chief hurdle to eradication of infection. In particular, it is thought that latently infected T cells can harbor integrated virus, which cannot be eliminated by current therapeutics. Therefore if therapy is discontinued for any reason, this reservoir rekindles infection. Additional potential reservoirs, such as macrophages or microglia in the brain could serve as long-lived sources of low-level virus production. It is thus imperative to identify and model means to eliminate these reservoirs. This proposal aims to use an in Vivo model, the recently described

Public Health Relevance

Latent or persistent HIV reservoirs are impervious to standard antiretroviral therapy, thus they stand as the chief obstacle to clearence of virus from the body. This project proposes to utilize a novel in vivo humanized mouse model to test strategies based on induction and subsequent targeted elimination of viral reservoirs. If successful, a new type of treatment strategy may be developed based on results obtained.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096113-03
Application #
8497439
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$349,965
Indirect Cost
$23,254

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

White, Cory H; Beliakova-Bethell, Nadejda; Lada, Steven M et al. (2018) Transcriptional Modulation of Human Endogenous Retroviruses in Primary CD4+ T Cells Following Vorinostat Treatment. Front Immunol 9:603
Chaillon, Antoine; Gianella, Sara; Lada, Steven M et al. (2018) Size, Composition, and Evolution of HIV DNA Populations during Early Antiretroviral Therapy and Intensification with Maraviroc. J Virol 92:
Jiang, Guochun; Nguyen, Don; Archin, Nancie M et al. (2018) HIV latency is reversed by ACSS2-driven histone crotonylation. J Clin Invest 128:1190-1198
Dubé, Karine; Dee, Lynda; Evans, David et al. (2018) Perceptions of Equipoise, Risk-Benefit Ratios, and ""Otherwise Healthy Volunteers"" in the Context of Early-Phase HIV Cure Research in the United States: A Qualitative Inquiry. J Empir Res Hum Res Ethics 13:3-17
Prakash, Katya; Gianella, Sara; Dubé, Karine et al. (2018) Willingness to participate in HIV research at the end of life (EOL). PLoS One 13:e0199670
Papasavvas, Emmanouil; Lada, Steven M; Joseph, Jocelin et al. (2018) Analytical ART interruption does not irreversibly change pre-interruption levels of cellular HIV. AIDS :
Honeycutt, Jenna B; Liao, Baolin; Nixon, Christopher C et al. (2018) T cells establish and maintain CNS viral infection in HIV-infected humanized mice. J Clin Invest 128:2862-2876
Power, Jennifer; Westle, Andrew; Dowsett, Gary W et al. (2018) Perceptions of HIV cure research among people living with HIV in Australia. PLoS One 13:e0202647
Marsden, Matthew D; Wu, Xiaomeng; Navab, Sara M et al. (2018) Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents. Virology 520:83-93
Beliakova-Bethell, Nadejda; Hezareh, Marjan; Wong, Joseph K et al. (2017) Relative efficacy of T cell stimuli as inducers of productive HIV-1 replication in latently infected CD4 lymphocytes from patients on suppressive cART. Virology 508:127-133

Showing the most recent 10 out of 221 publications